Detection of copy number disorders associated with congenital anomalies of the kidney and urinary tract in fetuses via single nucleotide polymorphism arrays

Cai, Meiying; Lin, Ning; Su, Linjuan; Wu, Xiaoqing; Xie, Xiaorui; Liu, Ying; Chen, Xuemei; Dai, Yifang; Lin, Yuan; Huang, Hailong; Xu, Liangpu

doi:10.1002/jcla.23025

Cited by 10 publications

(11 citation statements)

References 29 publications

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“…We conducted a retrospective study on RHD cases diagnosed prenatally by fetal ultrasound from the Prenatal Diagnosis Center of Fujian Provincial Maternal and Children Health Hospital, between January 2016 and July 2019. The inclusion criteria included the presence of a renal parenchymal defect such as renal agenesis or renal dysplasia (discovery of a small or cystic kidney for gestational age kidneys) (seven cases have been previously included in our papers such as case 1, case 2, case 8, case 9, case 12, case 13, and case 15) [5].…”

Section: Patient Datamentioning

confidence: 99%

“…Amniocentesis (in 74 cases) and umbilical cord blood collection (in 46 cases) were performed, according to gestational age. Amniotic fluid was collected by amniocentesis at 16-24 weeks of gestation, and fetal blood was collected by cordocentesis after 24 weeks of gestation [5]. The fetuses underwent routine ultrasonic scans, and fetal biometry was assessed at a median gestational age of 24 ± 6 weeks (range: 18 ± 2 to 34 ± 1 weeks).…”

Section: Patient Datamentioning

confidence: 99%

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Copy number variations associated with fetal congenital kidney malformations

Cai

Lin

et al. 2020

Mol Cytogenet

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Background: Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20-30% of all congenital malformations. Within the CAKUT phenotypic spectrum, renal hypodysplasia (RHD) is particularly severe. This study aimed to evaluate the applicability of single-nucleotide polymorphism (SNP) array test in prenatal diagnosis of RHD for improving prenatal genetic counseling and to search for evidence of a possible causative role of copy-number variations (CNVs) in RHD. Results: We performed a systematic survey of CNV burden in 120 fetuses with RHD: 103 cases were isolated RHD and 17 were non-isolated RHD. Single-nucleotide polymorphism (SNP) array test was performed using the Affymetrix CytoScan HD platform. All annotated CNVs were validated by fluorescence in situ hybridization. We identified abnormal CNVs in 15 (12.5%) cases of RHD; of these CNVs, 11 were pathogenic and 4 were variants of uncertain significance. The detection rate of abnormal CNVs in non-isolated RHD was higher (29.4%, 5/17) than that in isolated RHD (9.7%, 10/103) (P = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test. Conclusions: The variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases.

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Section: Patient Datamentioning

confidence: 99%

Section: Patient Datamentioning

confidence: 99%

Copy number variations associated with fetal congenital kidney malformations

Cai

Lin

et al. 2020

Mol Cytogenet

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“…A database of rare, pathogenic and likely pathogenic CNV regions identified in aggregate of CAKUT phenotypes has been populated through literature mining 4 , 10 – 14 (Online resource, Supplementary Table 1 ). Genomic coordinates have been defined in the hg19 assembly version.…”

Section: Methodsmentioning

confidence: 99%

“…The miRNA-centric approach was based on data from 153 patients with identified CAKUT-associated CNVs 4 to functionally interpret the most frequently affected miRNAs. The CNV-centric approach aimed to estimate the overall burden of CAKUT-associated CNVs on miRNA genes, by including all major studies investigating CNVs in CAKUT 4 , 10 – 14 . …”

Section: Methodsmentioning

confidence: 99%

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Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT

Mitrovic

Zivotic

Kolić

et al. 2022

Sci Rep

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Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA’s expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches.

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Review of genetic testing in kidney disease patients: Diagnostic yield of single nucleotide variants and copy number variations evaluated across and within kidney phenotype groups

Claus

Snoek

Knoers

et al. 2022

American J of Med Genetics Pt C

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Genetic kidney disease comprises a diverse group of disorders. These can roughly be divided in the phenotype groups congenital anomalies of the kidney and urinary tract, ciliopathies, glomerulopathies, stone disorders, tubulointerstitial kidney disease, and tubulopathies. Many etiologies can lead to chronic kidney disease that can progress to end-stage kidney disease. Despite each individual disease being rare, together these genetic disorders account for a large proportion of kidney disease cases. With the introduction of massively parallel sequencing, genetic testing has become more accessible, but a comprehensive analysis of the diagnostic yield is lacking. This review gives an overview of the diagnostic yield of genetic testing across and within the full range of kidney disease phenotypes through a systematic literature search that resulted in 115 included articles. Patient, test, and cohort characteristics that can influence the diagnostic yield are highlighted. Detection of copy number variations and their contribution to the diagnostic yield is described for all phenotype groups. Also, the impact of a genetic diagnosis for a patient and family members, which can be diagnostic, therapeutic, and prognostic, is shown through the included articles. This review will allow clinicians to estimate an a priori probability of finding a genetic cause for the kidney disease in their patients.

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Detection of copy number disorders associated with congenital anomalies of the kidney and urinary tract in fetuses via single nucleotide polymorphism arrays

Cited by 10 publications

References 29 publications

Copy number variations associated with fetal congenital kidney malformations

Copy number variations associated with fetal congenital kidney malformations

Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT

Review of genetic testing in kidney disease patients: Diagnostic yield of single nucleotide variants and copy number variations evaluated across and within kidney phenotype groups

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